Heart failure with preserved ejection fraction (HFPEF) is common and deadly but without
therapy. Inconclusive studies such as TOPCAT (Treatment of Preserved Cardiac Function Heart
Failure With an Aldosterone Antagonist) suggest spironolactone may be effective in HFPEF, but
it is generic and will not be studied by industry.
SPIRRIT is a unique Registry-Randomized Clinical Trial (RRCT) that will test the hypothesis
that spironolactone plus standard of care compared to standard of care alone reduces the
composite of CV mortality and HF hospitalization as follows:
Population: HFPEF patients in the Swedish Heart Failure Registry (2550 patients) and HFPEF
patients in US (650 patients). HFPEF defined as symptoms/signs of HF, elevated NTproBNP
(B-type Natriuretic Peptide; N-terminal pro b-type Natriuretic Peptide) and EF>=40%.
Intervention and control: Randomized 1:1 to intervention: spironolactone + usual care vs.
control: usual care alone.
Outcome: Primary outcome cardiovascular death or time to HF hospitalization. Secondary
outcomes include hospitalization for various causes, adverse events and treatment adherence.
In Sweden outcomes are obtained automatically by linking with the Population, Patient and
Drug Dispensed Registries. In the US, outcomes will be reported by sites and supplemented by
data from a call center. The trial is event-driven with enrollment 3 years and study duration
5 years. For the primary outcome (CV Death or first HF hospitalization) with an event target
of 632 events the sample size requires 3012 patients conservatively rounded to approximately
3200 patients. A detailed feasibility assessment shows that there will be > 8197 eligible
patients to meet the required enrollment of 3200 patients.